Aurora B is enriched at merotelic attachment sites, where it regulates MCAK
Aurora B is enriched at merotelic attachment sites, where it regulates MCAK
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DOI：
10.1016/j.cub.2006.07.057
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发表时间：
2006-09-05
期刊：
影响因子：
9.2
通讯作者：
Stukenberg, P. Todd
中科院分区：
文献类型：
--
作者：
Knowlton, Anne Lide;Lan, Weijie;Stukenberg, P. Todd
动点通常形成分生组织连接，其中一个动点连接到来自两个纺锤体极的微管上。这些连接可能导致不正确的染色体分离，并且是非整倍体的重要来源[1，2]，这是癌症的标志[3-5]。需要Aurora B激酶和Kinesin-13微管解聚酶有丝分裂着丝粒相关的Kinesin(MCAK)来释放不正确的微管附着[6-9]。Aurora B调节MCAK的活性和定位[10-12]。我们开始理解为什么MCAK和Aurora B在一些中期对齐的着丝粒中含量更多，而在大多数其他着丝粒中含量较低。我们发现Aurora B复合体的成员特定地富含在Merotelic附着点。我们还发现，Aurora B不需要其活性在这些位置变得丰富；然而，抑制Aurora B的活性会导致每个细胞的Merotelic连接数量显著增加。Aurora B的活性丰富了MCAK的Merotelic连接，并使MCAK在调节其微管解聚活性的残基上磷酸化。这些数据表明，解决缺陷的蛋白质特定地定位于Merotelic连接，在那里它们的酶活性受到调节。
Kinetochores often form merotelic attachments, in which a single kinetochore is attached to microtubules from both spindle poles. These attachments can result in improper chromosome segregation and are a significant source of aneuploidy [1, 2], a hallmark of cancer [3-5]. Aurora B kinase and the kinesin-13 microtubule depolymerase mitotic-centromere-associated kinesin (MCAK) are required to release improper microtubule attachments [6-9]. Aurora B regulates MCAK's activity and localization [10-12]. We set out to understand why MCAK and Aurora B are more abundant at some metaphase-aligned centromeres but are present at low amounts on most others. We found that members of the Aurora B complex are specifically enriched at merotelic attachment sites. We also found that Aurora B does not require its activity to become enriched at these sites; however, inhibition of Aurora B activity causes a significant increase in the number of merotelic attachments per cell. Aurora B activity enriches MCAK at merotelic attachments and phosphorylates MCAK on residues that regulate its microtubule depolymerase activity. These data demonstrate that proteins that resolve the defect are specifically localized to merotelic attachments, where their enzymatic activities are regulated.